Abstract
The mossy fibre pathway in the hippocampus uses glutamate as a neurotransmitter, but also contains the opioid peptide dynorphin. Synaptic release of dynorphin causes a presynaptic inhibition of neighbouring mossy fibres and inhibits the induction and expression of mossy fibre long-term potentiation. These findings demonstrate a physiological role for a neuropeptide in the central nervous system, provide a functional basis for the coexistence of a neuropeptide with classic neurotransmitters and demonstrate the very different roles played by these two classes of signalling molecules.
Similar content being viewed by others
References
Hökfelt, T. Neuron 7, 867–879 (1991).
Jan, L. Y. & Jan, Y. N. J. Physiol. 327, 219–246 (1982).
Jan, Y. N. & Jan, L. Y. Trends Neurosci. 6, 320–325 (1983).
Lundberg, J. M. & Hokfelt, T. Trends Neurosci. 6, 325–333 (1983).
Storm-Mathisen, J. et al. Nature 301, 517–520 (1983).
Crawford, I. L. & Connor, J. D. Nature 244, 442–443 (1973).
Gall, C. Brecha, N., Karten, H. & Chang, K.-J. J. comp. Neurol. 198, 335–350 (1981).
McGinty, J. F., Henriksen, S. J., Goldstein, A., Terenius, L. & Bloom, F. E. Proc. natn. Acad. Sci. U.S.A. 80, 589–593 (1983).
McLean, S., Rothman, R. B., Jacobson, A. E., Rice, K. C. & Herkenham, M. J. comp. Neurol. 255, 497–510 (1987).
Wagner, J. J., Evans, C. J. & Chavkin, C. J. Neurochem. 57, 333–343 (1991).
Terrian, D. M. et al. Brain Res. Bull. 21, 343–351 (1988).
Iwama, T., Ishihara, K., Satoh, M. & Takagi, H. Neurosci. Lett. 63, 190–194 (1986).
Caudle, R. M. & Chavkin, C. J. pharmac. Exp. Ther. 252, 1361–1369 (1990).
Goldstein, A. Trends pharmacol. Sci. 8, 456–459 (1987).
Chavkin, C., James, I. F. & Goldstein, A. Science 215, 413–415 (1982).
Takemori, A. E., Ho, B. Y., Naeseth, J. S. & Portoghese, P. S. J. Pharmac. exp. Ther. 246, 255–258 (1988).
Nicoll, R. A., Siggins, G. R., Ling, N., Bloom, F. E. & Guillemin, R. Proc. natn. Acad. Sci. U.S.A. 74, 2584–2588 (1977).
Zieglgansberger, W., French, E. D., Siggins, G. R. & Bloom, F. E. Science 205, 415–417 (1979).
Neumaier, J. F., Mailheau, S. & Chavkin, C. J. Pharmac. exp. Ther. 244, 564–570 (1988).
Lupica, C. R. & Dunwiddie, T. V. Synapse 8, 237–248 (1991).
Gillan, M. G. C. & Kosterlitz, H. W. Br. J. Pharmac. 77, 461–469 (1982).
Mosberg, H. I. et al. Proc. natn. Acad. Sci. U.S.A. 80, 5871–5874 (1983).
Nock, B., Giordano, A. L., Cicero, T. J. & O'Connor, L. H. J. Pharmac. exp. Ther. 254, 412–419 (1990).
Zukin, R. S., Eghbali, M., Olive, D., Unterwald, E. M. & Tempel, A. Proc. natn. Acad. Sci. U.S.A. 85, 4061–4065 (1988).
Zucker, R. S. A. Rev. Neurosci. 12, 13–31 (1989).
Katz, B. & Miledi, R. J. Physiol. 195, 481–492 (1968).
Mallart, A. & Martin, A. R. J. Physiol. 196, 593–604 (1968).
Creager, R., Dunwiddie, T. & Lynch, G. J. Physiol. 299, 409–424 (1980).
McFadzean, I., Lacey, M. G., Hill, R. G. & Henderson, G. Neuroscience 20, 231–239 (1987).
Gannon, R. L. & Terrian, D. M. Brain Res. 548, 242–247 (1991).
Kato, M., Chapman, C. & Bicknell, R. J. Brain Res. 574, 138–146 (1992).
Gauchy, C., Desban, M., Krebs, M. O., Glowinski, J. & Kemel, M. L. Neuroscience 41, 449–458 (1991).
Pinnock, R. D. Brain Res. 583, 237–246 (1992).
Wagner, J. J., Caudle, R. M. & Chavkin, C. J. Neurosci. 12, 132–141 (1992).
Bradler, J. E. & Barrionuevo, G. Neuroscience 35, 265–271 (1990).
Zalutsky, R. A. & Nicoll, R. A. Neurosci. Lett. 138, 193–197 (1992).
Martin, M. R. Neuropeptides 4, 45–50 (1983).
Zalutsky, R. A. & Nicoll, R. A. Science 248, 1619–1624 (1990).
Staubli, U., Larson, J. & Lynch, G. Synapse 5, 333–335 (1990).
Gross, R. A. & Macdonald, R. L. Proc. natn. Acad. Sci. U.S.A. 84, 5469–5473 (1987).
Bean, B. Nature 340, 153–156 (1989).
Adamson, P., Xiang, J.-Z., Mantzourides, T., Brammer, M. J. & Campbell, I. C. Eur. J. Pharmac. 174, 63–70 (1989).
Xiang, J.-Z., Adamson, P., Brammer, M. J. & Campbell, I. C. Neuropharmacology 29, 439–444 (1990).
Kamiya, R., Sawada, S. & Yamamoto, C. Neurosci. Lett. 91, 84–88 (1988).
Gallagher, M. in Opioids in the Hippocampus (eds McGinty. J. F. & Friedman, D. P.) 118–132 (NIDA Res. Monograph, 1988).
Decker, M. W. & McGaugh, J. L. Synapse 7, 151–168 (1991).
Collier, T. J. & Routtenberg, A. Brain Res. 310, 384–387 (1984).
Rolls, E. T. Cold Spring Harb. Symp. quant. Biol. 55, 995–1006 (1990).
Zalutsky, R. A. & Nicoll, R. A. in Transmitter Amino Acid Receptors: Structures, Transduction and Models for Drug Development Vol. 6 (Barnard, E. A. & Costa. E.) 415–422 (Thieme Medical, New York, 1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Weisskopf, M., Zalutsky, R. & Nicoll, R. The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation. Nature 362, 423–427 (1993). https://doi.org/10.1038/362423a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/362423a0
- Springer Nature Limited
This article is cited by
-
Exploring the Therapeutic Effect of Neurotrophins and Neuropeptides in Neurodegenerative Diseases: at a Glance
Molecular Neurobiology (2023)
-
Effects of Activation of κ-Opioid Receptors on Behavior during Postnatal Formation of the Stress Reactivity Systems
Neuroscience and Behavioral Physiology (2016)
-
Upregulated dynorphin opioid peptides mediate alcohol-induced learning and memory impairment
Translational Psychiatry (2013)
-
Targeting the Hippocampal Mossy Fiber Synapse for the Treatment of Psychiatric Disorders
Molecular Neurobiology (2009)
-
Gene polymorphisms in prodynorphin (PDYN) are associated with episodic memory in the elderly
Journal of Neural Transmission (2009)